High blood levels of LDL is an established cause for atherosclerosis and coronary heart disease. For selected patients, extracorporeal LDL removal is the most effective therapy. The goal of this project is to develop a monoclonal antibody-based immunoadsorption device capable of removing low density lipoprotein (LDL) from hypercholesterolemic whole blood circulated in a low pressure extracorporeal venous shunt. Phase I will extend studies demonstrating safety and efficacy of goat polyclonal antibody-based immunosorbents for removal of LDL from whole blood in vitro to the extracorporeal removal of LDL from whole blood of experimental animals. In addition, mouse anti-LDL monoclonal antibodies will be tested for their suitability in the LDL-immunosorbent device. Also, methods of chemical sterilization, immunosorbent regeneration, and storage between uses will be studied. During Phase II, advanced membrane technology, sorbent configuration, and coupling chemistry will be evaluated for improved immunosorbent efficacy and capacity. Extended human trials will begin with the identification of a safe and efficacious LDL-immunosorbent device prototype. During the course of these studies, new technology will be developed in three areas: (1) design of whole blood immunosorbents; (2) sterilization of immunosorbents; and (3) application of monoclonal antibodies to clinical immunosorbents.